Impact of the DNA Damage Response on Human Papillomavirus Chromatin.

Abstract

The fidelity of replication is regulated by the DNA damage response (DDR), an elaborate signaling network of proteins that detect, signal, and repair DNA lesions. While some viruses have evolved mechanisms to avoid or eliminate DNA repair machinery, others exploit the DDR to replicate their genomes [1]. Recent studies indicate that the DDR facilitates productive replication of human papillomaviruses (HPV) [2–8]. The ability of cells to detect and repair DNA breaks is dependent on the reorganization of surrounding chromatin [9]. The importance of histone post-translational modifications and chromatin remodeling proteins in recruitment of repair factors to DNA breaks is becoming increasingly clear. HPV genomes are histone-associated in the virion and exhibit a nucleosome pattern similar to that of cellular DNA in infected cells [10,11]. HPV chromatin is subject to histone modifications, likely important in ensuring the correct temporal expression of viral genes through the life cycle [12,13]. However, the assembly of DNA repair factors in large complexes at HPV replication centers raises the intriguing possibility that viral chromatin may also be subject to the changing chromatin dynamics associated with the DDR, facilitating efficient productive replication through DNA repair mechanisms.